This project is concerned with investigating the mechanism of polymerization of sickle hemoglobin. The points at which contact is established between individual hemoglobin tetramers within the polymeric structures will be looked for by an extension of a previously used technique in this laboratory. It consists of preparing hemoglobin hybrids, which contain both sickle beta-chains as well as additional mutations in the alpha-chains. The solubility properties of such double mutants can be used to provide a clue to the regions on the surface of the hemoglobin molecule which participate in the intermolecular contacts necessary for the formation of the rod-like helices, characteristic of sickle cell anemia. BIBLIOGRAPHIC REFERENCES: Benesch, R. Benesch, R.E., Yung, S. & Edalji, R., "Hemoglobin Covalently Bridged Across the Polyphosphate Binding Site" Biochem. Biophys. Res. Comm., 63:1123, 1975. Benesch, R.E., Yung, S., Benesch, R., Mack, J. & Schneider, R.G., "Alpha Chain Contacts in the Polymerization of Sickle Hemoglobin" Nature 260:219, 1976.